Ceraxa (nanoliposomal ceramide) / PendreaBio - LARVOL DELTA

KNAN2001: Study of C6 Ceramide NanoLiposome (CNL) in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=12 | Enrolling by invitation | Sponsor: Keystone Nano, Inc | Not yet recruiting ➔ Enrolling by invitation | Trial completion date: Oct 2026 ➔ Oct 2027 | Trial primary completion date: Jul 2026 ➔ Feb 2027

Enrollment open • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

KNAN2001: Study of C6 Ceramide NanoLiposome (CNL) in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=11 | Not yet recruiting | Sponsor: Keystone Nano, Inc | N=18 ➔ 11 | Trial completion date: Dec 2024 ➔ Oct 2026 | Trial primary completion date: Sep 2024 ➔ Jul 2026

Enrollment change • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Ceramide NanoLiposome in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Keystone Nano, Inc | Unknown status ➔ Completed | N=24 ➔ 14 | Trial completion date: Aug 2019 ➔ Nov 2023 | Trial primary completion date: Aug 2019 ➔ Aug 2023

Enrollment change • Metastases • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

KNAN2001: Study of C6 Ceramide NanoLiposome (CNL) in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Keystone Nano, Inc | Trial completion date: Jun 2022 ➔ Sep 2024 | Trial primary completion date: Dec 2021 ➔ Jul 2024

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A phase I study of the ceramide nanoliposome in patients with advanced solid tumors. (PubMed, Cancer Chemother Pharmacol) - P1 | "CNL exhibited an encouraging safety profile and pharmacokinetic parameters, with some signals of efficacy including prolonged stable disease in 1 patient with refractory pancreatic cancer. Pre-clinical data indicate potential synergy between CNL and multiple systemic therapies including chemotherapy, targeted therapy, and immunotherapy. Future studies are planned investigating CNL in combination strategies."

Journal • Metastases • P1 data • Constipation • Fatigue • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pain • Pancreatic Cancer • Solid Tumor

KNAN2001: Study of C6 Ceramide NanoLiposome (CNL) in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Keystone Nano, Inc | Trial completion date: Sep 2024 ➔ Dec 2024

Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Correlation of survival outcomes with progression heterogeneity in patients (pts) treated with pembrolizumab (pembro). (ASCO 2018) - P1,P2; "...All KN001 findings were confirmed in KN052. Similar analyses will be shown for pts with NSCLC in KN010 (pembro vs docetaxel). These analyses suggest there may be distinct populations of PD phenotypes with unique survival outcomes. RECIST v1.1 does not fully capture these PD phenotypes and may not accurately identify treatment failure."

Clinical • Heterogeneity • Bladder Cancer • Melanoma • Non Small Cell Lung Cancer

Correlation of survival outcomes with progression heterogeneity in patients (pts) treated with pembrolizumab (pembro). (ASCO 2018) - P1,P2; "...All KN001 findings were confirmed in KN052. Similar analyses will be shown for pts with NSCLC in KN010 (pembro vs docetaxel). These analyses suggest there may be distinct populations of PD phenotypes with unique survival outcomes. RECIST v1.1 does not fully capture these PD phenotypes and may not accurately identify treatment failure."

Clinical • Heterogeneity • Bladder Cancer • Melanoma • Non Small Cell Lung Cancer

Pivotal Dose of Pembrolizumab - A Dose Finding Strategy for Immuno-Oncology. (PubMed, Clin Pharmacol Ther) - "Despite numerous publications emphasizing the value of dose finding, drug development in oncology is dominated by the mindset that higher dose provides higher efficacy. Simulations showed that 200 mg Q3W can achieve ≥90% TE in clinically relevant scenarios resulting in the recommendation of 200 mg Q3W as RP2D. Randomized dose comparison studies (KN001 B2 and D) showing similar efficacy over 5-fold dose/exposure range confirmed RP2D as the pivotal dose."

IO biomarker • Journal • Oncology

KNAN2001: Study of C6 Ceramide NanoLiposome (CNL) in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1; N=18; Not yet recruiting; Sponsor: Keystone Nano, Inc

Clinical • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

"4y OS KN001. 27% alive at 48m in 1st line cohort; 16% in prob treated #ASCO18 #lcsm" (@DrRiyazShah)

Lung Cancer • Oncology • Solid Tumor

Pan-tumor analysis of the association of cancer and immune biology-related gene expression signatures with response to pembrolizumab monotherapy (SITC 2019) - "Studies with available RNASeq data (N=1188) included: KN001/KN006-Melanoma (N=476; pembrolizumab-treated and ipilimumab-naive), KN052-urothelial (N=186), KN012/KN055-HNSCC (N=147; HPV-negative by whole exome sequencing), KN086-TNBC (N=132), KN059-Gastric (N=92), and KN427-RCC (N=78), KN100-Ovarian (N=77). Pan-cancer testing of exploratory gene expression signatures using the RNASeq platform in 1188 patients from single-arm pembrolizumab trials suggests that features beyond interferon gamma-related T-cell inflammation may be relevant to response to anti-PD1 monotherapy and may define other axes of tumor biology as rational candidates for pembrolizumab combinations. These features (Angiogenesis, mMDSC and Stroma/EMT/TGFβ) have been previously hypothesized to represent immune-suppressive axes with potential negative impact on immunotherapy efficacy. Future evaluation of the association of these signatures with response and survival outcomes in other cancer types and in..."

IO Biomarker • Monotherapy • PD(L)-1 Biomarker • IFNG

Outcomes of advanced melanoma patients who discontinued pembrolizumab (pembro) after complete response (CR) in the French early access program (EAP) (ESMO 2019) - "Background: Information on outcomes after cessation of anti-PD-1 mAb for CR are scarce outside KN-001 & 006 trials...Of note, 10% of these 68 pts had >3 metastatic sites, 10% had brain metastases, 53% had 2010 AJCC stage M1c melanoma, and 67% had received previous treatment for advanced melanoma (mainly ipilimumab)... In this large real-life cohort, 10% of pts reached CR and discontinued pembro. All but 3% were recurrence-free after a median 15.3 m of treatment, thus validating the discontinuation of anti-PD1 in complete responders. Clinical trial identification: CCTIRS, #15.640."

Clinical • IO Biomarker • PD(L)-1 Biomarker

"JCO paper on KN001 5-yr survival data.... https://t.co/weNhdnCYhc" (@bpiperdi)

Ceramide NanoLiposome in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Keystone Nano, Inc; Trial completion date: Mar 2019 ➔ Aug 2019; Trial primary completion date: Mar 2019 ➔ Aug 2019

Clinical • Trial completion date • Trial primary completion date